16-15395986-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001128423.2(MPV17L):​c.89C>T​(p.Ala30Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000542 in 1,513,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

MPV17L
NM_001128423.2 missense

Scores

2
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.901
Variant links:
Genes affected
MPV17L (HGNC:26827): (MPV17 mitochondrial inner membrane protein like) Involved in negative regulation of hydrogen peroxide biosynthetic process; negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; and reactive oxygen species metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.39747816).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MPV17LNM_001128423.2 linkc.89C>T p.Ala30Val missense_variant Exon 1 of 4 ENST00000396385.4 NP_001121895.1 Q2QL34-1
MPV17L-BMERB1NM_001414674.1 linkc.89C>T p.Ala30Val missense_variant Exon 1 of 6 NP_001401603.1
MPV17LNM_173803.4 linkc.89C>T p.Ala30Val missense_variant Exon 1 of 3 NP_776164.2 Q2QL34-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MPV17LENST00000396385.4 linkc.89C>T p.Ala30Val missense_variant Exon 1 of 4 1 NM_001128423.2 ENSP00000379669.3 Q2QL34-1
ENSG00000261130ENST00000568766.1 linkc.89C>T p.Ala30Val missense_variant Exon 1 of 2 2 ENSP00000454340.1 H3BMD7

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000186
AC:
2
AN:
107814
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
59536
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000494
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000573
AC:
78
AN:
1361326
Hom.:
0
Cov.:
31
AF XY:
0.0000566
AC XY:
38
AN XY:
670894
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000719
Gnomad4 OTH exome
AF:
0.0000176
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000511
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 15, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.89C>T (p.A30V) alteration is located in exon 1 (coding exon 1) of the MPV17L gene. This alteration results from a C to T substitution at nucleotide position 89, causing the alanine (A) at amino acid position 30 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.074
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
18
DANN
Uncertain
1.0
DEOGEN2
Benign
0.030
.;T;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.89
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.79
T;T;T
M_CAP
Pathogenic
0.64
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-0.34
T
MutationAssessor
Benign
1.2
L;L;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-2.1
N;N;N
REVEL
Uncertain
0.30
Sift
Benign
0.29
T;D;D
Sift4G
Uncertain
0.019
D;T;D
Polyphen
0.94
P;P;.
Vest4
0.16
MutPred
0.38
Loss of disorder (P = 0.0893);Loss of disorder (P = 0.0893);Loss of disorder (P = 0.0893);
MVP
0.24
MPC
2.3
ClinPred
0.63
D
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.11
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1269806399; hg19: chr16-15489843; API